Clinical Trials /

Phase 1/2 Study of APR-246 in Combination With Pembrolizumab in Subjects With Solid Tumor Malignancies

NCT04383938

Description:

A phase 1/2, open-label, study to determine the safety and preliminary efficacy of APR-246 in combination with pembrolizumab in subjects with solid tumor malignancies. The study will include a safety lead-in portion followed by a phase 2 expansion portion in specific disease groups.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Bladder Carcinoma
  • Gastric Carcinoma
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase 1/2 Study of APR-246 in Combination With Pembrolizumab in Subjects With Solid Tumor Malignancies
  • Official Title: Study of APR-246 in Combination With Pembrolizumab in Subjects With Solid Tumor Malignancies

Clinical Trial IDs

  • ORG STUDY ID: A20-11195
  • NCT ID: NCT04383938

Conditions

  • Bladder Cancer
  • Gastric Cancer
  • Non Small Cell Lung Cancer
  • NSCLC
  • Urothelial Carcinoma
  • Advanced Solid Tumor

Interventions

DrugSynonymsArms
APR-246 (eprenetapopt) + PembrolizumabExpansion 1

Purpose

A phase 1/2, open-label, study to determine the safety and preliminary efficacy of APR-246 in combination with pembrolizumab in subjects with solid tumor malignancies. The study will include a safety lead-in portion followed by a phase 2 expansion portion in specific disease groups.

Detailed Description

      This is a phase 1/2, open-label, study to determine the safety and preliminary efficacy of
      APR-246 (eprenetapopt) in combination with pembrolizumab in subjects with solid tumor
      malignancies. In the safety lead-in part of study (phase 1), the safety and the recommended
      phase 2 dose (RP2D) of APR-246 will be investigated.

      In the expansion part of the study (phase 2), both safety and efficacy for the combination
      therapy will be investigated in the 3 cohorts.
    

Trial Arms

NameTypeDescriptionInterventions
Safety Lead InExperimentalPatients with advanced solid tumors. Up to 3 dose levels evaluated.
  • APR-246 (eprenetapopt) + Pembrolizumab
Expansion 1ExperimentalPatients with advanced gastric cancer.
  • APR-246 (eprenetapopt) + Pembrolizumab
Expansion 2ExperimentalPatients with advanced urothelial/bladder cancer.
  • APR-246 (eprenetapopt) + Pembrolizumab
Expansion 3ExperimentalPatients with advanced NSCLC.
  • APR-246 (eprenetapopt) + Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          1. Signed informed consent form (ICF) and ability to comply with protocol requirements.

          2. Known tumor TP53 mutation status from recent or archival sample.

          3. Histologically and/or cytologically confirmed solid tumor malignancy

               1. Safety lead in- Advanced non-central nervous system (CNS) primary tumors that
                  have progressed after first line treatment, who are intolerant to first line
                  treatment, or who are unable to receive first line treatment, and for whom
                  pembrolizumab, or pembrolizumab-based therapy is considered appropriate

               2. Expansion 1- Patients with a confirmed diagnosis of advanced gastric or
                  gastroesophageal junction (GEJ) tumors that have progressed after first line
                  treatment, who are intolerant to first line treatment, or who are unable to
                  receive first line treatment

               3. Expansion 2- Patients with a confirmed diagnosis of advanced bladder/urothelial
                  tumors that have progressed after first line treatment, or who are intolerant to
                  first line treatment, or who are unable to receive first line treatment with
                  cisplatin-based chemotherapy.

               4. Expansion 3- Confirmed diagnosis of advanced non-small cell lung cancer (NSCLC)
                  previously treated with anti-PD-1 or anti-PD-L1 therapy.

          4. Adequate organ function

               1. Creatinine clearance > 30 mL/min

               2. Total serum bilirubin < 1.5 × upper limit of normal (ULN) unless due to Gilbert's
                  syndrome, tumor involvement, hemolysis or considered an effect of regular blood
                  transfusions

               3. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3 × ULN,
                  unless due to involvement by the underlying malignancy.

          5. Projected life expectancy of ≥ 12 weeks.

          6. Age ≥ 18 years at the time of signing the ICF.

          7. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2

          8. In the expansion portion, measurable disease meeting the following criteria:

               1. At least 1 lesion of ≥10 mm in the longest diameter (LD) for a non-lymph node or
                  ≥15 mm in the short-axis diameter for a lymph node that is serially measurable
                  according to RECIST 1.1.

               2. Lesions that have had external beam radiotherapy or loco-regional therapies such
                  as radiofrequency ablation must show subsequent evidence of substantial size
                  increase (ex. 20% increase in LD) to be deemed a target lesion.

          9. Negative serum or urine pregnancy test prior to study treatment initiation in female
             subjects of childbearing potential.

         10. Women of childbearing potential and men with female partners of childbearing potential
             must be willing to use an effective form of contraception

        Exclusion Criteria:

          1. Known history of untreated human immunodeficiency virus (HIV)/HIV with a detectable
             viral load or active hepatitis B or active hepatitis C infection.

          2. Cardiac abnormalities

          3. Concomitant malignancies or previous malignancies with less than a 1-year disease-free
             interval at the time of signing consent.

          4. Pregnancy or lactation.

          5. Active uncontrolled systemic infection.

          6. An autoimmune condition requiring ≥ 10 mg (or equivalent corticosteroid) prednisone
             daily, or any other systemic immunosuppressive treatment within 28 days of first dose
             of study therapy.

          7. Known history of active tuberculosis.

          8. Current (non-infectious) pneumonitis, or a history of pneumonitis that required
             steroids.

          9. A live vaccine administered within 30 days of the first dose of study treatment.

         10. Receipt of any investigational product within 14 days or 5 half-lives prior to study
             treatment initiation, whichever is shortest.

         11. Prior intolerance to pembrolizumab or other anti-PD-1/PD-L1 agents.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:To evaluate the safety and tolerability of APR-246 in combination with pembrolizumab in subjects with solid tumors.
Time Frame:Through study completion, approximately 1 year
Safety Issue:
Description:To determine the occurrence of dose limiting toxicities (DLTs), classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events Frequency of treatment-emergent adverse events (TEAEs), and serious adverse events (SAEs) related to APR-246 in combination with pembrolizumab.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Aprea Therapeutics

Trial Keywords

  • Pembrolizumab
  • APR-246
  • Aprea
  • eprenetapopt

Last Updated

May 11, 2020